1. SECONDARY AMENORRHEA
Dr Hanaa Alani

2. Is the absence or abnormal cessation of the menses
AMENORRHEA
Is the absence or abnormal cessation of the menses
PHYSIOLOGIAL
AMENORRHEA
PATHOLOGIAL
AMENORRHEA

3. CONTROL OF MENSTRUAL CYCLE
HYPOTHALAMUS
PITUITARY
ENDOCRINE
OVARIAN
OUTFLOW TRACT
AXIS

4. CLASSIFICATION OF AMENORRHEA
Pre-puberty
Pregnancy related
Menopause
Primary
Secondary

5. AMENORRHEA PATHOLOGICAL AMENORRHEA
A patient is diagnosed with primary amenorrhea if she has not reached menarche by age 16 with normal secondary sexual characteristics.
Secondary amenorrhea if established menses have ceased for longer than 6 months without any physiological reasons.

6. Secondary Amenorrhea
Secondary amenorrhea is the absence of menstrual periods for 6 months in a woman who had previously been regular.

7. Secondary Amenorrhea - Physiological -
The most common cause of secondary amenorrhea in reproductive age women is pregnancy and this should always be excluded by physical exam and laboratory testing for the pregnancy hormone - HCG.

8. Secondary Amenorrhea - ETIOLOGY -
ENDOCRINE
HYPOTHALAMUS-PITUITARY
Pituitary tumour
Sheehan’s
syndrome
Hypothalamic
dysfunction
Hypothyroidism
Cushing’s
Adrenal tumour
Ovarian tumour
(androgen)
OVARIAN
Premature ovarian
failure
PCOS
Surgical removal
Asherman’s
syndrome
Hysterectomy
OUTFLOW TRACT

9. Secondary Amenorrhea/Oligomenorrhea: Etiology
Most common etiologies:
Ovarian disease – 40%
Hypothalamic dysfunction – 35%
Pituitary disease – 19%
Uterine disease – 5%
Other – 1%

10. Secondary Amenorrhea/Oligomenorrhea: Etiology
Pregnancy
Thyroid disease
Hyperprolactinemia
Prolactinoma
Breastfeeding, Breast stimulation
Medication (i.e. Antipsychotics, Antidepressants)
Hypergonadotropic hypogonadism
Postmenopausal ovarian failure
Premature ovarian failure
Hypogonadotropic hypogonadism
Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa)
CNS tumor (i.e. Craniopharyngioma)
Sheehan’s syndrome
Chronic illness
Normogonadotropic
Outflow tract obstruction (i.e. Asherman’s syndrome, Cervical stenosis)
Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease, CAH)

11. Secondary Amenorrhea - ETIOLOGY -
HYPOTHALAMIC CAUSES
Hypothalamic dysfunction is a common cause (30%).
It is more often seen as a result of stress, weight loss
and eating disorders
It may be due to tumour, infarction, thrombosis or
inflammation.

12. Secondary Amenorrhea - ETIOLOGY -
PITUITARY CAUSES
Pituitary failure - It is usually the acquired type as the result of trauma, treatment of pituitary tumour or
infarction after massive blood loss ( Sheehan’s syndrome )
Pituitary tumour  hyperprolactinaemia which cause secondary amenorrhea.

13. Secondary Amenorrhea - ETIOLOGY -
ENDOCRINE CAUSES
Thyroid disorder and Cushing’s disease interfere with the normal functioning of the hypothalamic -pituitary – ovarian axis  present with amenorrhea.
High level of thyroxine inhibit FSH release.
Androgen – secreting tumours of the ovaries  cause secondary amenorrhea.

14. Secondary Amenorrhea - ETIOLOGY -
ANATOMICAL CAUSES
Usually due to previous surgery.
Commonest example:
1). Hysterectomy
2). Endometrial ablation
3). Asherman’s syndrome (damage to the
endometrium with adhesion formation)
4). Stenosis of the cervix following cone biopsy

15. 1-Uterine defect Asherman`s syndrome This is intrauterine synechiae
*withdrawal beeding after hormonal test is negative
*history of D&C after delivery or termination of pregnancy other cauese TB or schistosomiasis
*normal ovulatory cycle & premenstrual symptoms
Patients with Asherman`s syndrome may evaluated by HSG & transvaginal US
TREATMENT
*hysteroscopic treatment with excision of synechiae
*mainaining of seperation of uterine walls by insertion of a large inert IUCD such as a Lippes loop
The result of treatment are often disappointing in term of subsequent fertility

16. Secondary Amenorrhea - ETIOLOGY -
PREMATURE OVARIAN FAILURE
Premature ovarian failure occurs in about 1% before
the age of 40.
Premature ovarian failure may be due to:
1). Chemotherapy and radiotherapy.
2). Autoimmune disease following viral infection
3). Following surgery for conditions such as
endometriosis

17. Treatment of premature ovarian failure
Ovarian failure before 40 years
Ovarian failure before 30 years may be due to chromosomal disorders . Karyotyping is done to check for mosaicism ( some cells have Y chromosme) gonadectomy is indicated to prevent malignant transformation
Other causes of premature ovarian failure
Ovarian injury from surgery, radiation or chemotherapy, galactocaemia &autoimmunity
When premature ovarian failure is secondary to autoimmunity other endocrine organs could be affected
Investigations
FBS for diabetes
Free thyroxine, TSH for hypothyroidism
Serum calcium for hypoparathyroidism
Fasting morning cortisol
Treatment of premature ovarian failure
By hormone therapy (estrogen & progesterone)

18. Secondary Amenorrhea - ETIOLOGY -
DRUGS CAUSING HYPERPROLACTINAEMIA
Hyperprolactinaemia accounts for 20% of cases of amenorrhea.
Prolactin inhibits GnRH release from the hypothalamus
Drugs may cause hyperprolactinaemia:

19. 3-Amenorrhea with hyperprolactinaemia
Galactorrhea is the most frequently observed abnormalities associated with hyperprolactinemia
Hyperprolactinemia that is sever or associated with menstrual disturbances or galactorhea should be confirmed by a second test, TSH should be tested for hypothyroidism
If clinically significant hyperprolactinaemia is not explained by hypothyroidism or drug use a CT or MRI scan of sella turcica should be performed
Drugs that may cause hyperprolactinaemia includes
1-tranqulizers
2-antidepressants
3-antihypertensives
4-narcotics
5-metaclopramide

20. Mechanisms that produce  Prolactin
1 - Normally dopamine suppresses prolactin production. If a mass compresses the stalk of the pituitary, the dopamine feedback pathway is interrupted and it can no longer inhibit prolactin   prolactin levels. Also,GnRH will not be able to pass through and there will be  LH and  FSH. If there is  prolactin and  LH & FSH
there may be  E2 (Estradiol) levels - consider hormone replacement therapy.
2 - Hyperprolactinemia may also be caused by psychoactive drugs which suppress dopamine. Even so, you will still see  FSH & LH levels.
3 - Prolactin secreting adenomas produce excess prolactin   levels

21. Two types of Prolactin Secreting Adenomas
Microadenomas vs. Macroadenomas
< 10 mm > 10 mm diagnosed on MRI –
important to do Associated with visual symptoms
Very benign and headaches
Treat symptoms only – amenorrhea Must be treated
Follow up MRIs every 1-2 yrs to check surgical treatment
Bromocriptine agonist –
may shrink adenoma for additional growth
Radiation - works well but may cause panhypopituitarism.

22. Treatment of Hyperprolactinemia
Dopamine agonist therapy - (Cabegolin,Bromocriptine) - most common. This should induce ovulation and shrink the adenoma. With drug induced hyperprolactinemia, bromocriptine may counter the effects of the anti-depressent medications.
If it is a macroadenoma, transphenoidal resection may be done. This will result in
resumption of ovulation for 40% of patients. Only 10-50% will have a long tercure with the surgery.
Response to radiation can be very slow.
If a patient has a microadenoma or other causes of hyperprolactinemia, birth control pills may be used to bring on regular periods and to correct the galactorrhea. If a woman wants to try and have a baby you can try ovulation induction.
Goals of Treatment: regulate menses, prevent endometrial hyperplasia, induce ovulation for pregnancy, improve hirsutism (excessive body hair in a masculine pattern of distribution due to hereditary or hormonal factors.)

23. Secondary Amenorrhea - ETIOLOGY -
POLYCYSTIC OVARIAN SYNDROME (PCOS)
PCOS accounts for 90% of cases of oligoamenorrhea
Also known as Stein-Leventhal syndrome
The etiology is probably related to insulin resistance,
with a failure of normal follicular development and
ovulation
The classical picture – AMENORRHEA, OBESE,
SUBINFERTILITY and HIRSUITISM

24. THE ASSESSMENT
HISTORY
EXAMINATION
INVESTIGATIONS

25. ASSESSMENT
The most common cause of secondary amenorrhea in reproductive age women is pregnancy and this should always be excluded by physical exam and laboratory testing for the pregnancy hormone - HCG.

26. ASSESSMENT
History
A good history can reveal the etiologic diagnosis in up to 85% of cases of amenorrhea.

27. CLINICAL ASSESSMENT - HISTORY -
ASK ABOUT
Menstrual cycle  age of menarche and previous menstrual history
Previous pregnancies - severe PPH (Sheehan’s syndrome)
Weight change  A large amount of weight loss (anorexia nervosa)
Hot flashes , decreased libido  premature menopause
Certain medications
Contraception
Associate symptoms - Cushing's disease , hypothyroidism
Previous gynaecological surgery
Chronic illness

28. CLINICAL ASSESSMENT - EXAMINATION -
CHECK FOR
BODY MASS INDEX (BMI)  weight loss-related amenorrhea
BLOOD PRESSURE  elevated in Cushing and PCOS
ANDROGEN EXCESS  hirsuitism (PCOS) – virilization (tumour)
Secondary sexual characteristic
Breast examination  may revealed galactorrhea,
Abdominal (haemato mera) and pelvic masses (ovarian tumour)
Inspection of genitalia  cervical stenosis

29. If the history and physical exam are suggestive of a certain etiology
CLINICAL ASSESSMENT - INVESTIGATIONS -
If the history and physical exam are suggestive of a certain etiology
The workup can sometimes be more directed

30. CLINICAL ASSESSMENT - INVESTIGATIONS -
Some patients will not demonstrate any obvious etiology for their amenorrhea on history and physical examination
These patients can be worked up in a logical manner using a stepwise approach.

31. INVESTIGATING SECONDARY AMENORRHEA
The most common cause of secondary amenorrhea in reproductive age women is pregnancy and this should always be excluded by physical exam and laboratory testing for the pregnancy hormone - HCG.

32. INVESTIGATING SECONDARY AMENORRHEA
Once pregnancy has been excluded
Progesterone challenge test
TSH (thyroid stimulating hormone)
FSH, LH
Prolactin level

33. Secondary Amenorrhea/Oligomenorrhea: Evaluation
Progestin challenge test
Medroxyprogesterone acetate 10 mg daily for 10 days
IF withdrawal bleed occurs – Not outflow tract obstruction
IF no withdrawal bleed occurs – Estrogen/Progestin challenge test
Estrogen/Progestin challenge test
Oral conjugated estrogen – 2.5 mg daily for 35 days
Medroxyprogesterone acetate 10 mg daily for days
IF no withdrawal bleed occurs – Endometrial scarring
Hysterosalpingogram or Hysteroscopy to evaluate endometrial cavity

34. INVESTIGATING SECONDAY AMENORRHEA
NEGATIVE PREGNANCY TEST
FSH, LH and Thyroid function test Progesterone challenge test
WITHDRAWAL
BLEEDING
NO WITHDRAWAL
BLEEDING
HYPOESTROGENIC
COMPROMISED OUTFLOW TRACT
ANOVULATION
Positive E-P
challenge test
Negative E-P
challenge test
FSH normal + high LH  PCOS
High prolactin  pituitary tumour
Normal or Low FSH
Very high FSH
Normal FSH
Ovarian Failure
Asherman’s syndrome
(HSG or hysteroscopy)
Hypothalamic-pituitary failure

35. Secondary Amenorrhea/Oligomenorrhea: Evaluation
Evaluation of hyperandrogenism
Symptoms: hirsutism, acne, alopecia, masculinization, and virilization
Differential diagnosis:
Adrenal disorders: Atypical congenital adrenal hyperplasia (CAH), Cushing’s syndrome, Adrenal neoplasm
Ovarian disorders: PCOS, Ovarian neoplasms
Lab: Testosterone, DHEA-S, 17α-hydroxyprogesterone
Hormone
Level
Indication
Testosterone
< 200 ng/dL
PCOS
> 200 ng/dL
Evaluate for adrenal or ovarian tumor
DHEA-S
< 700 ng/dL
> 700 ng/dL
17α-hydroxyprogesterone
> 4 ng/mL
Consider ACTH stimulation test to diagnose CAH

36. Ovarian failure (premature menopause)
SECONADARY AMENORRHEA
Ovarian failure (premature menopause)
chromosomal anomalies
autoimmune disease
If the woman is under 30, a karyotype should be performed to rule out any mosaicism involving a Y chromosome.
it is prudent to screen for thyroid, parathyroid, and adrenal dysfunction
If a Y chromosome is found the gonads should be surgically excised.
Laboratory evidence of autoimmune phenomenon is much more prevalent than clinically significant disease

37. Hypothalamic-pituitary failure
SECONDARY AMENORRHEA
Hypothalamic-pituitary failure
Patients who do not bleed after the progestin challenge
But do bleed after estrogen/progestin and
Have normal or low FSH and LH levels

38. INVESTIGATING SECONDARY AMENORRHEA
INVESTIGATIONS
DIAGNOSIS
SITE OF DISORDER
FSH, LH and estradiol - Low
Hypothalamic – failure
Weight-related amenorrhea
HYPOTHALAMUS
Prolactin – High
FSH, LH and estradiol – Low
FSH, LH and estrogen - Low
Pituitary adenoma
Sheehan syndrome
PITUITARY
TSH – raised ; T4 – low or N
Hypothyroidism
ENDOCRINE
FSH, LH – high ; E2 – low
FSH – Normal ; LH - High
Premature menopause
PCOS
OVARY
EPCT – negative
HSG / Hystereoscopy
Asherman’s syndrome
MULLERIAN TRACT

39. TREATMENT OF AMENORRHEA
The need for treatment depends on
Underlying causes
Need for regular periods
Trying to conceive (fertility
Need for contraception)

40. TREATMENT OF AMENORRHEA
TRYING TO CONCEIVE
The prognosis for women with confirmed ovarian failure is poor.
ANOVULATION  response well with ovulation induction treatment
PCOS  ovulation may resume with weight reduction – fertility drugs
- use of gonadotrophins or ovarian drilling.
HYPERPROLACTINAEMIA  respond to treatment with dopamine
agonist.
HYPOTHALAMIC DYSFUNCTION  maintenance of normal weight
and change of lifestyle
ASHERMAN’S syndrome  breaking down adhesion + insert IUCD

41. TREATMENT OF AMENORRHEA
WANT REGULAR PERIOD
The use of
1): COMBINED ORAL CONTRACEPTIVE
2): HRT
NEED CONTRACEPTION
Confirmed ovarian failure will not required contraception
Women requiring contraception  oral contraceptives are
method of choice

42. Amenorrhea/Oligomenorrhea: Management
Diagnosis
Management
Ovarian insufficiency
Premature ovarian failure
Postmenopausal ovarian failure
Hormone replacement therapy (HRT)
*Congenital anatomic lesions
Surgical correction
*Presence of Y chromosome (i.e. AIS)
Gonadectomy
*Gonadal dysgenesis (i.e. Turner syndrome)
Estrogen + progestin, growth hormone
IVF (IF pregnancy desired)
Hyperprolactinemia
Dopamine agonist (Bromocriptine, Cabergoline)
Functional hypothalamic amenorrhea
Increase caloric intake > energy expenditure
Hypothalamic or pituitary dysfunction
(non-reversible)
OCP’s, pulsatile GnRH or exogenous gonadotropins
CNS tumor
Craniopharyngioma
Prolactinoma
Surgical resection
Microadenoma (< 10mm) – Dopamine agonist
Macroadenoma (>10mm) – Trans-sphenoidal resection
PCOS
OCP’s, weight loss, and metformin
Asherman’s syndrome
Hysteroscopic lysis of adhesions
*Causes of primary amenorrhea only

43. Treatment goals of amennorrhea and oligomenorrhea include prevention of complications such as osteoporosis, endometrial hyperplasia and heart disease; preservation of fertility; and in primary amenorrhea, progression of normal pubertal development

44. THANK
YOU